Hydrochloric Acid → Dimethylol glycol

HRID 72812

Reaction equation

HRID 72812 reaction equation
CC1C=C[C:5]([C:6](NC2C=C(C(F)(F)F)C=C(N3C=C(C)N=C3)C=2)=[O:7])=CC=1NC1N=C(C2C=NC=CC=2)C=CN=1.Cl.Cl.[CH3:42][C:43]1[CH:67]=[CH:66][C:46]([C:47]([NH:49][C:50]2[CH:55]=[C:54]([C:56]([F:59])([F:58])[F:57])[CH:53]=[C:52]([N:60]3[CH:64]=[C:63]([CH3:65])[N:62]=[CH:61]3)[CH:51]=2)=[O:48])=[CH:45][C:44]=1[NH:68][C:69]1[N:74]=[C:73]([C:75]2[CH:76]=[N:77][CH:78]=[CH:79][CH:80]=2)[CH:72]=[CH:71][N:70]=1.[OH2:81].[CH3:82][OH:83]>>[CH2:6]([O:7][CH2:47][OH:48])[CH2:5][O:81][CH2:82][OH:83].[CH3:42][C:43]1[CH:67]=[CH:66][C:46]([C:47]([NH:49][C:50]2[CH:55]=[C:54]([C:56]([F:57])([F:58])[F:59])[CH:53]=[C:52]([N:60]3[CH:64]=[C:63]([CH3:65])[N:62]=[CH:61]3)[CH:51]=2)=[O:48])=[CH:45][C:44]=1[NH:68][C:69]1[N:74]=[C:73]([C:75]2[CH:76]=[N:77][CH:78]=[CH:79][CH:80]=2)[CH:72]=[CH:71][N:70]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887Methanol3×HCID 962WaterHCID 644241NilotinibHCID 16006490Nilotinib Hydrochloride Anhydrous

Product 2

HCID 62511Dimethylol glycolHCID 644241Nilotinib

Conditions

Temperature
42 °C

Procedure

4.0 g 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide free base is dissolved in 60 mL methanol at 50° C. 1.05 equivalent (688.7 μL) of hydrochloric acid is added as a solution in 2 mL of methanol. The solution is let stand for 60 minutes at 50° C. The solution is cooled down to 42° C. and kept at this temperature for 15 minutes. A suspension of 4 mg of 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide hydrochloride in methanol (40 mg)/water (0.4 mg) homogenized for 10 seconds in an ultrasonic bath is added. The suspension is let stand for 2.5 hours at 42° C., then cooled down in 7 hours at 20° C. The suspension remains at 20° C. for 56 hours. The suspension is not filtrated before analysis. The dimethanol solvate form SB of the hydrochloride salt of 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide is obtained.

Workup

  1. customfor 60 minutes
  2. customat 50° C
  3. additionis added
  4. customfor 2.5 hours
  5. customat 42° C.
  6. temperaturecooled down in 7 hours at 20° C
  7. waitThe suspension remains at 20° C. for 56 hours
  8. filtrationThe suspension is not filtrated before analysis

Sources & evidence

ORD record
ord-c9e451e93dcf46ad9018867018349a8c
Source dataset
uspto-grants-2014_09
Patent number
US08829015B2

Linked notes

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